Dosulepin hydrochloride

Dosulepin

Clinical data
Trade names	Prothiaden, others
Synonyms	IZ-914, KS-1596, dothiepin (USAN US)
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: C
Routes of administration	Oral
ATC code	N06AA16 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	30%
Protein binding	84%
Metabolism	Hepatic (N-demethylation, S-oxidation, glucuronidation)
Metabolites	Northiaden, dothiepin sulfoxide, northiaden sulfoxide, glucuronide conjugates
Biological half-life	Dothiepin: 14.4–23.9 hours Dothiepin sulfoxide: 22.7–25.5 hours Northiaden: 34.7–45.7 hours Northiaden sulfoxide: 24.2–33.5 hours
Excretion	Urine: 56% Feces: 15%
Identifiers
IUPAC name (3E)-3-(6H-benzo[c][1]benzothiepin-11-ylidene)-N,N-dimethylpropan-1-amine
CAS Number	25627-37-6 Y ^ (E isomer) 25627-36-5 (E isomer HCl) 113-53-1 (racemate) 897-15-4 (racemate HCl)
PubChem CID	5284550
ChemSpider	4447605 N
UNII	W13O82Z7HL
KEGG	D07872 Y
ChEBI	CHEBI:36803 N
ChEMBL	CHEMBL108947 N
ECHA InfoCard	100.003.665
Chemical and physical data
Formula	C19H21NS
Molar mass	295.444 g/mol
3D model (JSmol)	Interactive image
SMILES CN(C)CC/C=C/1\C2=CC=CC=C2CSC3=CC=CC=C31
InChI InChI=1S/C19H21NS/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12H,7,13-14H2,1-2H3/b17-11+ N Key:PHTUQLWOUWZIMZ-GZTJUZNOSA-N N
NY (what is this?)

Dosulepin, also known as dothiepin and sold under the brand name Prothiaden among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression. Dosulepin was once the most frequently prescribed antidepressant in the United Kingdom, but it is no longer widely used due to its relatively high toxicity in overdose without therapeutic advantages over other TCAs. It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) and also has other activities including antihistamine, antiadrenergic, antiserotonergic, anticholinergic, and sodium channel-blocking effects.

Dosulepin is used for the treatment of major depressive disorder. There is clear evidence of the efficacy of dosulepin in psychogenic facial pain, though the drug may be needed for up to a year.

Contraindications include:

Common adverse effects:

Less common adverse effects:

The symptoms and the treatment of an overdose are largely the same as for the other TCAs. Dosulepin may be particularly toxic in overdose compared to other TCAs. The onset of toxic effects is around 4–6 hours after dosulepin is ingested. In order to minimise the risk of overdose it is advised that patients only receive a limited number of tablets at a time so as to limit their risk of overdosing. It is also advised that patients are not prescribed any medications that are known to increase the risk of toxicity in those receiving dosulepin due to the potential for mixed overdoses. The medication should also be kept out of reach of children.

Dosulepin can potentiate the effects of alcohol and at least one death has been attributed to this combination. TCAs potentiate the sedative effects of barbiturates, tranquilizers and CNS depressants.Guanethidine and other adrenergic neuron blocking drugs can have their antihypertensive effects blocked by dosulepin. Sympathomimetics may potentiate the sympathomimetic effects of dosulepin. Due to the anticholinergic and antihistamine effects of dosulepin anticholinergic and antihistamine medications may have their effects potentiated by dosulepin and hence these combinations are advised against. Dosulepin may have its postural hypotensive effects potentiated by diuretics. Anticonvulsants may have their efficacy reduced by dosulepin due to its ability to reduce the seizure threshold.